Embedded Files
Overview of the classes and roles of non-coding RNAs in cancer. Taken from Dragomir et al. 2020 Gut.
Non-coding RNAs in cancer
While once considered "junk DNA," non-coding RNAs have begun to gain attention in recent years for their role in multiple diseases. Examples from three main classes of non-coding RNAs, microRNAs, long non-coding RNAs (lncRNA), and circular RNA (circRNA), have been found to possess tumor-suppressive or oncogenic properties. Understanding how these crucial molecules contribute to cancer and how we can leverage them for cancer treatments remains a very active field of study. My work focuses on lncRNAs and circRNAs regulated by the p53 family members (an essential group of tumor-suppressive proteins) in lung adenocarcinoma.
Annotations of the YWHAQ gene and nearby lncRNAs in the mouse (top) and human (bottom) genomes using the UCSC Genome Browser. Red arrows indicate positionally conserved lncRNAs.
Finding conserved circRNA & lncRNA
The nucleic acid sequences of non-coding genes, which give rise to non-coding RNAs, are typically under a lower selection pressure than protein-coding genes. Therefore, we focus on their relative position in the genome to identify lncRNAs and circRNAs found in mouse models and human patients. This positional conservation (synteny or collinearity) may indicate functional roles for these non-coding RNAs. For example, the lncRNAs marked with the red arrows in the nearby image occur in the same relative position (next to the YWHAQ gene and on the opposite DNA strand) despite having almost no similarity at the sequence level. Filtering our preliminary data to focus on the conserved non-coding RNAs allows us to identify the best potential candidates for further investigation.
Affinity purification of circRNAs uses probes complementary to the unique backsplice junction to pulldown the circRNA and its interacting RNAs and proteins.
Identifying interacting proteins and RNAs
We assess candidate non-coding RNAs for oncogenic or tumor-suppressive function. We use multiple assays in the lab, such as transwell invasion, apoptosis resistance, and proliferation assays. We also verify these effects using xenograft mouse models. The next step is to determine how these non-coding RNAs affect cells. We use affinity purification to identify which proteins or other RNAs in the cell interact with our candidate non-coding RNA. The putative interactors are then examined with follow-up assays to establish the molecular mechanism by which the non-coding RNA impacts the cells.
Page updated
Google Sites
Report abuse